BackgroundNegative symptoms of schizophrenia impose a substantial burden on society， and the current antipsychotic drugs have limited efficacy in treating these symptoms. Intermittent theta burst stimulation （iTBS）， as a novel neuromodulation technique， shows potential therapeutic promise. However， the evidence for its efficacy in treating negative symptoms of schizophrenia and its relationship with associated immuno-inflammatory changes remain to be further elucidated. ObjectiveTo investigate the efficacy of iTBS targeting the left dorsolateral prefrontal cortex （L-DLPFC） on persistent negative symptoms of schizophrenia， and to analyze its relationship with changes in peripheral blood inflammatory markers， so as to provide references for the clinical application of iTBS in treating persistent negative symptoms and to offer clues for further research into its potential biological mechanisms. MethodsA randomized， double-blind， sham-controlled clinical trial was conducted. A total of 60 patients with schizophrenia who were hospitalized at Xuzhou Oriental Peopple's Hospital from February 20， 2024 to May 10， 2025 were consecutively enrolled. All patients met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and fulfilled the criteria for persistent negative symptoms. Participants were randomly assigned into the study group and the control group， with 30 patients in each group. The two groups respectively received 20 sessions of either active iTBS or sham stimulation over a 4-week period. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale （PANSS） at the baseline， the end of treatment， and 3 months after treatment. Peripheral blood inflammatory markers were measured at the baseline and at the end of treatment， including white blood cell count， platelet count， neutrophil count， lymphocyte count， and monocyte count， the neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， and platelet-to-lymphocyte ratio （PLR） were also calculated. A linear mixed model was used to compare PANSS scores between the two groups. Spearman correlation analysis was performed to examine the association between reductions in inflammatory markers at the end of treatment and reductions in PANSS negative symptom subscale scores， with body mass index （BMI） and chlorpromazine-equivalent dose as covariates. Results①The time-group interaction effect for the PANSS negative symptom subscale score was statistically significant （F=5.410， P<0.01）. At the end of treatment and 3 months after treatment， the study group had significantly lower scores on the PANSS negative symptom subscale than the control group （P<0.01）. ② At the end of treatment， group differences in reduction scores for neutrophil count， NLR， and PLR were significant （Z=-2.262， -2.048， -2.070， P<0.05）. However， after FDR correction， the between-group differences in reductions in peripheral blood inflammatory markers were no longer statistically significant （P>0.05）. ③ After adjusting for BMI and chlorpromazine equivalents， the reduction in PANSS negative symptom subscale scores was positively correlated with the reduction in neutrophil count in the study group （r_s=0.382， P=0.045）. ConclusioniTBS targeting the L-DLPFC may be beneficial in improving persistent negative symptoms of schizophrenia， and its clinical efficacy may be associated with changes in neutrophil count. ［Funded by National Natural Science Foundation of China （number， 82371510）； Social Development Project of Jiangsu Province （number， BE2023668）. www.chictr.org.cn number， ChiCTR2500101060］

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Autophagy, a highly conserved and lysosome-dependent intracellular catabolic process, plays an important role in maintaining cellular homeostasis and adapting to various cellular stresses. Autophagy receptor involved in autophagy is more selective and effective in recognising and degrading protein aggregates and dysfunctional or redundant organelles in cells, especially pathogens invading into the cells, in order to maintain the homeostasis of the organism; Some viruses can also antagonise or take hostage autophagy receptor, and make use of autophagy to target the degradation of host proteins, thereby increasing their self-infection. In this paper, we review the structure and function of autophagy receptors, and discuss the role of viruses that use autophagy receptors to proliferate and infect the host, so as to provide references for the development of related viral diseases and the search for specific antiviral therapeutic targets.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Objective To explore the aesthetic effect of adsorptive denture restoration on completely edentulous patients and the im-pact on masticatory function and language function.Methods A study was conducted from June 2020 to June 2023 among 85 com-pletely edentulous patients.The patients were randomly divided into 2 groups.The routine group(n=43)underwent traditional com-plete denture restoration,while the observation group(n=42)underwent adsorptive denture restoration.Comparison was made between groups on the success rate of denture restoration,adaptation time,satisfaction with denture restoration,aesthetic effect,masticatory function,language function,retention stability,comfort level,the OHIP-14 scores before restoration and at 6 months after restoration,frequencies of follow-up visits and adjustments,and the incidence of complications.Results Compared with the routine group,the ob-servation group had a significantly higher success rate of one-time denture wearing,significantly shorter adaptation time and significantly higher satisfaction with restoration,with statistically significant differences(P＜0.05).After restoration,height of the lower face(Sn-Gn)increased significantly,while the midface to lower face ratio(G-Sn/Sn-Gn)and nasolabial angle(Cm-Sn-Ls)decreased signifi-cantly in both groups.The changes of Sn-Gn,G-Sn/Sn-Gn and Cm-Sn-Ls in the observation group after restoration were significantly greater(P＜0.05).Bite force,masticatory efficiency,language function score,retention stability score and wearing comfort level score of the observation group were significantly higher(P＜0.05).After restoration,the scores for physiological function,psychological func-tion and activities of daily living of the two groups decreased significantly.The observation group had significantly lower life quality scores(P＜0.05).The frequencies of follow-up visits and adjustments and the total incidence of complications were significantly lower in obser-vation group(P＜0.05).Conclusion Compared with traditional complete denture restoration,adsorptive denture restoration can achieve more obvious aesthetic effect on completely edentulous patients,and improve the basic function of dentures more significantly.In addition,adsorptive denture restoration has characteristics of shorter adaptation time,better prognosis and lower risk of complications.

Sepsis poses a significant threat to hu-man health due to its widespread prevalence,high mortality rate,substantial treatment costs,and the absence of effective life-saving therapies.Melato-nin,a primary hormone regulating the circadian rhythm,has demonstrated potential as a promising therapeutic agent against sepsis.Its anti-inflamma-tory,antioxidant,immunomodulatory,mitochondri-al protective,and multi-organ protective effects are noteworthy.In this review,we summarize current research on the mechanisms of action and clinical efficacy of melatonin in sepsis treatment and multi-organ function preservation,aiming to offer new perspectives and support for sepsis research and therapy.

Delirium is an acute brain dysfunction syndrome,mainly manifested by cognitive impairment and mental abnormalities.It is the most common manifestation of brain dysfunction associated with severe diseases.Critically ill patients with delirium often have poor prognosis,but there is currently no"miracle drug"for the prevention and treatment of delirium in clinical practice.Melatonin is an endogenous neurohormone secreted by the pineal gland,which has the functions of regulating sleep circadian rhythm,anti-inflammatory,antioxidant,and neuroprotective.When delirium occurs in critically ill patients,the serum melatonin level often changes,indicating that melatonin may be involved in the occurrence and development of delirium.Current research suggests that exogenous supplementation of melatonin may have a preventive and therapeutic effect on delirium.This article reviews researches on the mechanism and clinical efficacy of melatonin in the prevention and treatment of delirium in critically ill patients,with the aim of providing reference for basic and clinical research on the prevention and treatment of delirium in critically ill patients.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To explore the aesthetic effect of adsorptive denture restoration on completely edentulous patients and the im-pact on masticatory function and language function.Methods A study was conducted from June 2020 to June 2023 among 85 com-pletely edentulous patients.The patients were randomly divided into 2 groups.The routine group(n=43)underwent traditional com-plete denture restoration,while the observation group(n=42)underwent adsorptive denture restoration.Comparison was made between groups on the success rate of denture restoration,adaptation time,satisfaction with denture restoration,aesthetic effect,masticatory function,language function,retention stability,comfort level,the OHIP-14 scores before restoration and at 6 months after restoration,frequencies of follow-up visits and adjustments,and the incidence of complications.Results Compared with the routine group,the ob-servation group had a significantly higher success rate of one-time denture wearing,significantly shorter adaptation time and significantly higher satisfaction with restoration,with statistically significant differences(P＜0.05).After restoration,height of the lower face(Sn-Gn)increased significantly,while the midface to lower face ratio(G-Sn/Sn-Gn)and nasolabial angle(Cm-Sn-Ls)decreased signifi-cantly in both groups.The changes of Sn-Gn,G-Sn/Sn-Gn and Cm-Sn-Ls in the observation group after restoration were significantly greater(P＜0.05).Bite force,masticatory efficiency,language function score,retention stability score and wearing comfort level score of the observation group were significantly higher(P＜0.05).After restoration,the scores for physiological function,psychological func-tion and activities of daily living of the two groups decreased significantly.The observation group had significantly lower life quality scores(P＜0.05).The frequencies of follow-up visits and adjustments and the total incidence of complications were significantly lower in obser-vation group(P＜0.05).Conclusion Compared with traditional complete denture restoration,adsorptive denture restoration can achieve more obvious aesthetic effect on completely edentulous patients,and improve the basic function of dentures more significantly.In addition,adsorptive denture restoration has characteristics of shorter adaptation time,better prognosis and lower risk of complications.